ABSTRACT
Objective:To summarize the clinical features and pathological changes of peripheral tissues from patients with neuronal intranuclear inclusion disease (NIID) diagnosed by genetic tests.Methods:Repeat-primed polymerase chain reaction was used to confirm the GGC repeated expansion in the 5′ untranslated region of the NOTCH2NLC gene in patients with suspected NIID who had visited the Department of Neurology of Peking University First Hospital from January 2018 to February 2020. The clinical data and pathological changes of peripheral tissues from patients with genetically diagnosed NIID were collected retrospectively and analysed. Immunostaining with anti-p62 and anti-ubiquitin antibody was performed on peripheral biopsy specimens.Results:Totally nine patients with NIID who had GGC repeated expansion in the NOTCH2NLC gene were found. Five patients were familial (from three faimilies), and four patients were sporadic. The age of onset was 36-61(51.33±7.12) years. The most common symptoms in this NIID group were episodic emotion and personality change (8/9), paroxysmal disturbance of consciousness (6/9) and intermitant head discomfort (6/9). Other symptoms included cognitive dysfunction, limb weakness, limb sensory disturbance, bladder dysfunction, ataxia, seizures and psychiatric symptoms. Brain magnetic resonance imaging showed high signals along the corticomedullary junction on diffusion-weighted image in eight out of nine patients. Skin biopsied samples from nine patients demonstrated the presence of eosinophilic intranuclear inclusions (IIs), appearing in the nucleus of fibroblasts, fat cells and ductal epithelial cells of sweat glands on hematoxylin-eosin staining. IIs were positive on anti-p62 and anti-ubiquitin immunostaining. Electron microscopy indicated the IIs were composed of a pile of filament materials without membrane. Muscle biopsies from two patients showed no obvious neurogenic or myogenic pathologic changes, except in one patient several rimmed vacuoles fibers were found. In one patient sural nerve biopsy showed severe demyelinating pathological changes. No IIs were found in the muscles and peripheral nerve tissue either by histological examination or by immunohistochemical staining with anti-p62 or anti-ubiquitin, while IIs were found by immunofluorescence staining with both anti-p62 and anti-ubiquitin in three patient′s tissue. Conclusions:The phenotype of this NIID patient group is adult-onset NIID, with episodic encephalopathy as the main clinical manifestation. Skin biopsy has high pathological diagnostic value for NIID. The immunofluorescence staining with anti-p62 and anti-ubiquitin is easier to detect the presence of IIs than histological staining and immumohistochemical staining.
ABSTRACT
Tremor is a common movement disorder,but its etiological identification and clinical diagnosis pose a certain difficulty due to its complex clinical manifestations,various types,requirement of multidisciplinary knowledge,and similar symptoms shared by many other causes and diseases.In recent years,many advances in the clinical classification,diagnosis and treatment of tremor have been published and will help us better understand tremor and improve the diagnosis and treatment of tremor.
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Objective To discuss the clinical features of dystonia manifested as Parkinsonism ( PKS) . Methods Clinical materials of a patient with dystonia manifested as PKS were analyzed retrospectively. Results The onset age of the young women was 31 years old, who was started asymmetrically with symptoms of claudication and tremor of the right foot. Levodopa had a short-term effect. The results of dopamine transporter ( DAT) PET showed that DAT in retrolentiform part were decreased significantly. Atypical Parkinson's disease was considered and she was treated as PKS long-termly. Subsequently, heterozygous mutation of c. 268-4T>A (NM_018105) in DYT6 gene was found through the next-generation sequencing, which was a kind of splicing mutation and confirmed by the first-generation sequencing. Conclusions Patients with dystonia might share similar clinical manifestations with PKS. Particularly, they should be differentiated with young-onset Parkinson's disease combined with focal dystonia. Clinical observation and genetic testing are important approaches to differentiate them.
ABSTRACT
Multiple system atrophy(MSA) can be easily misdiagnosed as Parkinson's disease (PD) or other forms of atypical Parkinsonism,because they not only share similar pathological changes but also present many common clinical manifestations,which make early diagnosis difficult.How to better identify MSA plays a decisive role in subsequent treatment and should concern physicians.The aim of this review is to examine the autonomic nervous dysfunction and its early clinical manifestations,detection methods,and imaging characteristics of MSA,and thus to provide helpful guidelines for the early diagnosis of MSA.